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新的长链脂肪酸受体G-蛋白偶联受体120(G-protein-coupled receptor120,GPR120)是2型糖尿病的潜在治疗靶标.由于其晶体结构迄今尚未获得,成为基于结构的新药设计的瓶颈.首先,以人体β2肾上腺能素受体(human β2 adrenergic receptor,β2AR)晶体结构为模板,通过同源模建方法构建GPR120三维结构,对整个体系进行包膜的分子动力学模拟.然后采用分子对接技术模建了GPR120的小分子激动剂GW9508与GPR120的相互作用模型,发现了受体分子识别的关键性残基,为开展定点突变实验提供了指导意义.所建模型为研究受体与配体作用提供了合理的初始结构,此方法也适用于其他G蛋白偶联受体的分子模建.
G-protein-coupled receptor 120 (GPR120), a new long-chain fatty acid receptor, is a potential therapeutic target for type 2 diabetes, a bottleneck in structural-based drug design because its crystal structure has so far not been obtained First of all, based on the human β2 adrenergic receptor (β2AR) crystal structure as a template, the three-dimensional structure of GPR120 was constructed by homology modeling and the whole system was simulated by molecular dynamics simulation.And then, Docking technology modeled GPR120 small molecule agonist GW9508 and GPR120 interaction model and found the key residues of the receptor molecule recognition, to provide guidance for the site-directed mutagenesis experiments.The model for the study of receptor and with The role of the body provides a reasonable initial structure, this method also applies to other G protein-coupled receptors molecular modeling.